The Epidermal Growth Factor Receptor (EGFR) is a validated therapeutic target for the treatment of many cancers. However, the inhibition of EGFR has proven effective only in a limited subset of patients1.
The limitations of these cancer therapeutics may be due to the fact that the therapeutics aim to inhibit the tyrosine kinase activity of EGFR. A recent study showed that the knockdown of EGFR with small interfering RNA led to cell death in an autophagic process, independently of EGFR receptor tyrosine kinase activity2. Accordingly, the inhibition of EGFR tyrosine kinase activity alone is likely insufficient to cause cytotoxicity of EGFR driven tumors.
A further drawback of some EGFR-targeted cancer therapeutics currently used in the clinical setting is that drug resistance often develops after initial use of the therapeutic. For example, while non-small cell lung cancer is initially sensitive to erlotinib, resistance develops upon subsequent administrations of this drug.
In view of the foregoing, there exists a need for a cancer therapeutic that targets EGFR in a manner other than inhibition of EGFR tyrosine kinase activity. There also exists a need for a therapeutic that treats cancer without drug resistance developing after initial use.